1. Field of Invention
The field of the currently claimed embodiments of this invention relates to systems, methods and components for isolating cells from a fluid sample.
2. Discussion of Related Art
The most common causes of cancer-related death in patients occur when solid tumors metastasize. While the molecular mechanisms of cancer metastases are still largely unknown, there is a considerable body of evidence indicating that tumor cells are shed from a primary tumor mass at the earliest stages of malignant progression (Kaiser, J. Medicine. Cancer's circulation problem. Science 327, 1072-4 (2010); Bernards, R. & Weinberg, R.A. A progression puzzle. Nature 418, 823 (2002); Criscitiello, C., Sotiriou, C. & Ignatiadis, M. Circulating tumor cells and emerging blood biomarkers in breast cancer. Current Opinion in Oncology 22, 552-8 (2010)). These ‘break-away’ cancer cells enter the blood stream and travel to different tissues of the body as the cellular origin of metastases (Pantel, K. & Brakenhoff, R. H. Dissecting the metastatic cascade. Nature Reviews Cancer 4, 448-56 (2004)). The cells that escape from the primary tumor are known as circulating tumor cells (CTCs) (Pantel, K. & Alix-Panabieres, C. Circulating tumour cells in cancer patients: challenges and perspectives. Trends in Molecular Medicine 16, 398-406 (2010)). The gold standard for determining tumor status is through the histopathology analysis of biopsy samples. In early stage metastasis or recurrence, it is difficult to identify the metastatic/recurrence sites for biopsy.
CTCs can be regarded as the “liquid biopsy” of the tumor, thus providing convenient access to tumor cells, and earlier access to potentially fatal metastases. However, detection and characterization of CTCs have been technically challenging due to the extremely low abundance (a few to hundreds per mL) of CTCs among a high number (109 cells/mL) of hematologic cells (Racila, E., Euhus, D., Weiss, A. J., Rao, C., McConnell, J., Terstappen, L. W. M. M. & Uhr, J. W. Detection and characterization of carcinoma cells in the blood. Proceedings of the National Academy of Sciences of the United States of America 95, 4589-4594 (1998); Zieglschmid, V., Hollmann, C. & Bocher, 0. Detection of disseminated tumor cells in peripheral blood. Critical Reviews in Clinical Laboratory Sciences 42, 155-96 (2005)). It has been established that the variation of CTC number over the course of treatment period was found to be an independent predictor of therapeutic outcomes, progression-free and overall survival (Cristofanilli, M., Budd, G. T., Ellis, M. J., Stopeck, A., Matera, J., Miller, M. C., Reuben, J. M., Doyle, G. V., Allard, W. J., Terstappen, L. W. & Hayes, D. F. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. The New England journal of medicine 351, 781-91 (2004)) of solid-tumor patients. Further, molecular analyses of these CTCs found in cancer patients may yield critical genomic, proteomic, or metabolomic information that could steer effective treatment of the cancer patient.
Although many technologies are available to immobilize CTCs, they lack the ability to isolate the single CTCs free from a background of non-specifically captured white blood cells (WBCs) for subsequent molecular and functional analysis (e.g., whole genome sequencing, RT-PCR). Therefore, there remains a need for improved devices and methods to isolate rare cells such as CTCs from whole blood and/or other bodily fluids.